Studies designed to assess the potential role of endogenous interferon(s) (IFN) on macrophage function have ben underway for several months. The first phase of this project has focused on the capacity for human monocytes to produce interferon(s) and the regulation of that production. We have found that freshly isolated human monocytes do not produce interferon in response to bacterial lipopolysaccharide (LPS) but can be primed to respond to LPS for IFN production by prior treatment with either granulocytemacrophage colony stimulating factor (GM-CSF) or interferon- gamma IFN-gamma. This regulation of IFN production under these circumstances is under current investigation, but preliminary results suggest that it is transcriptionally regulated. Macrophage colony stimulating factor (M-CSF) is not active as a priming agent, although it preserves the survival of monocytes in culture. GM-CSF and IFN-gamma synergize for priming, suggesting two distinct pathways are being utilized. Pilot studies with anti-IFN-alpha receptor antibodies indicate that this receptor is also upregulated by GM-CSF treatment of monocytes. Further studies are being designed to assess the significance of these alternations in monocyte gene expression on host defense functions controlled by IFNs.